Targetable alterations in primary extranodal diffuse large B‐cell lymphoma

Abstract

Primary extranodal diffuse large B-cell lymphoma (PE-DLBCL) is a heterogeneous subgroup of DLBCL. We investigated the prevalence and prognostic value of surface expression of PD-L1, PD1, and CD30, copy number of 9p24.1 (PD-L1 region), and mutations in MYD88, CD79B, CARD11, and BTK in a cohort of 116 patients, localized in the mediastinum (PMBL, n = 12), ear, nose and throat (ENT, n = 28), central nervous system (n = 29), testis (n = 7), breast (n = 4), stomach (n = 10), bone (n = 8), spleen (n = 2), and skin (n = 16). PD-L1 expression is most frequent in PMBL (92%), followed by lymphomas originating in the stomach (57%), ENT (23%), and skin (18%). PD1 was expressed at low levels in less than 13% of PE-DLBCL, while CD30 expression was found in 58% of PMBL. Mutation analysis revealed an unexpectedly high frequency of MYD88 and CD79B mutations in ENT lymphomas (46% and 50%, respectively).CARD11 mutations are rare but more frequently found in gastric lymphomas (30%), suggesting BTK resistance. Thirty-four of 113 (30%) of the lymphomas harbored both MYD88 and CD79B mutations. Lower overall and progression-free survival rates were found for cases with MYD88, CD79B, and BTK mutations. These data confirm the biologic singularity of PE-DLBCLs and provide some suggestions for targeted therapies.

Response rates of extra‐nodal diffuse large B cell lymphoma to anti‐CD19‐CAR T cells: A real word retrospective multicenter study

“…DLBCL can present with nodal or extra-nodal involvement. Extra-nodal(EN) lymphoma is considered clinically, genetically and prognostically distinct from nodal lymphoma(ND) [1][2][3][4] . A retrospective study revealed that EN DLBCL was associated with older age and poorer performance status 3 .…”

Primary Cutaneous B-Cell Lymphomas with Large Cell Morphology: A Practical Review

“…Alterations of PDL1/2 locus (9p24.1) are present in a variable number of cases, mainly as relative gain. Relative loss and polysomy of 9p24.1 have also been reported [ 32 ].…”

“…Molecular findings of PCDLBCL, NOS are not entirely known, and it is debatable whether the molecular landscape of this neoplasm is significantly different from systemic DLBCL. Weissinger Se et al have recently indagated the molecular alteration in a series of primary extranodal lymphomas, including 16 PCDBCL, NOS [ 32 ]. The most common mutated genes in PCDLBCL, NOS were MYD88 (50%), CD79B (37%), CARD11 (6%), and BTK (6%).…”

“…MYD88 and CD79B mutations are involved in B-cell receptor (BCR) activation and are significantly associated with a non-GC phenotype in accordance with Hans algorithm. In addition, MYD88 mutation seems to be significantly associated with a worse prognosis [ 32 , 33 ]. Alterations of PDL1/2 locus (9p24.1) are present in a variable number of cases, mainly as relative gain.…”

EFNB1 level affects drug response in DLBCL cell lines

“…The genetic hallmarks of MCD subtype included MYD88 L265P , CD79B mutations, leading to activation of B-cell receptor (BCR) signaling pathway, and deletion of tumor suppressor gene CDKN2A. Extranodal lymphoma mainly belonged to the MCD subtype (5,6).…”